Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation

Michal Mokry, Arjan Boltjes, Lotte Slenders, Gemma Bel-Bordes, Kai Cui, Eli Brouwer, Joost M. Mekke, Marie A.C. Depuydt, Nathalie Timmerman, Farahnaz Waissi, Maarten C. Verwer, Adam W. Turner, Mohammad Daud Khan, Chani J. Hodonsky, Ernest Diez Benavente, Robin J.G. Hartman, Noortje A.M. van den Dungen, Nico Lansu, Emilia Nagyova, Koen H.M. PrangeJason C. Kovacic, Johan L.M. Björkegren, Eleftherios Pavlos, Evangelos Andreakos, Heribert Schunkert, Gary K. Owens, Claudia Monaco, Aloke V. Finn, Renu Virmani, Nicholas J. Leeper, Menno P.J. de Winther, Johan Kuiper, Gert J. de Borst, Erik S.G. Stroes, Mete Civelek, Dominique P.V. de Kleijn, Hester M. den Ruijter, Folkert W. Asselbergs, Sander W. van der Laan, Clint L. Miller, Gerard Pasterkamp

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved subphenotyping. Here, we analyzed the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Furthermore, we did a preliminary analysis of potential circulating biomarkers that mark the different plaque phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.

Original languageEnglish
Pages (from-to)1140-1155
Number of pages16
JournalNature Cardiovascular Research
Volume1
Issue number12
DOIs
StatePublished - Dec 2022

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